title: IL-16 induces intestinal inflammation via PepT1 upregulation in a pufferfish model: new insights into the molecular mechanism of inflammatory bowel disease.
abstract: Inflammatory bowel disease (IBD) has long been a worldwide health care problem with a persistently increasing incidence. Although its clinical features have been well described, its etiology and pathogenesis remain unclear. IL-16 is a chemoattractant cytokine with various effects on cellular activities and diseases. However, the involvement of IL-16 in IBD remains poorly understood. In this study, to our knowledge we report for the first time the mechanism by which IL-16 induces intestinal inflammation by upregulating the expression of oligopeptide transporter member 1 (PepT1) in a Tetraodon nigroviridis fish model. The dextran sodium sulfate-induced colitis model in this species revealed that IL-16 levels significantly increase accompanied by elevations in PepT1 in the colon. Moreover, the signs of colitis were dramatically attenuated by IL-16 depletion using anti-IL-16 Abs. In vivo IL-16 administration induced remarkable intestinal inflammation with typical ulcerative colitis-like features, including histologic damage, inflammatory cell infiltration, increased myeloperoxidase activity, and proinflammatory cytokines expression, which corresponded with significant PepT1 upregulation in the colon. The IL-16-induced PepT1 expression and its upregulated fMLF transport were also demonstrated in vitro. To our knowledge, our study provides the first evidence of the connection between IL-16 and PepT1, which provides new insights into the molecular mechanism underlying IBD development. Additionally, this study suggests that fish species are an attractive model for studying IBD. By providing a better understanding of IL-16 biology from fish to mammals, this study should aid the development of IL-16-based therapies for IBD.
authors.affiliation: College of Life Sciences, Zhejiang University, Hangzhou 310058, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Yi-qi
authors.initials: YQ
authors.lastname: Lu
authors.forename: Yi
authors.initials: Y
authors.lastname: Wen
authors.forename: Dai-yong
authors.initials: DY
authors.lastname: Yu
authors.forename: Liang
authors.initials: L
authors.lastname: Ge
authors.forename: Wei-ren
authors.initials: WR
authors.lastname: Dong
authors.forename: Li-xin
authors.initials: LX
authors.lastname: Xiang
authors.forename: Jian-zhong
authors.initials: JZ
authors.lastname: Shao
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D045744:Cell Line, Tumor; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D006367:HeLa Cells; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000378:metabolism*; D019410:Interleukin-16 / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D007422:Intestines / Q000276:immunology*; D000074011:Peptide Transporter 1; D034622:RNA Interference; D034741:RNA, Small Interfering; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D023721:Tetraodontiformes / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000906:Antibodies; D019410:Interleukin-16; D000074011:Peptide Transporter 1; D034741:RNA, Small Interfering; D027981:Symporters; D016264:Dextran Sulfate